Incidence and Clinical Characteristics of Genetic Disorders Detected Through Expanded Newborn Screening at Queen Sirikit National Institute of Child Health in Thailand: A 4-Year Retrospective Analysis

Expanded newborn screening (eNBS) using tandem mass spectrometry (MS/MS) optimizes outcomes for inborn errors of metabolism (IEMs). Following Thailand’s universal eNBS rollout, we evaluated the 4-year diagnostic performance, disease spectrum, and operational challenges of a major regional screening center. This retrospective cohort study evaluated 202,305 neonates screened at the Queen Sirikit National Institute of Child Health (2022–2025). The protocol transitioned from an in-house LC-MS/MS assay to a commercial non-derivatized kit featuring succinylacetone quantification. Screening interpretation was optimized using secondary analyte ratios and R4S/CLIR scoring systems. Fifty-five infants were confirmed with an on-panel IEM (birth incidence 1:3678). Median turnaround time was at 7 days of age. The initial screen identified 51 true-positive cases, restricting the program false-positive rate to 0.15%, while eight presumptive positive individuals were lost to follow-up. Three citrullinemia type 2 cases were captured via routine second screening, and one clinical tyrosinemia type 1 case was missed during the early in-house assay phase. The regional hub demonstrated robust diagnostic performance and efficiency within Thailand’s universal healthcare framework. While post-analytical algorithms successfully optimize specificity, the identification of initial false negatives highlights the necessity of repeat screening in vulnerable populations—such as low birth weight or small-for-gestational-age infants—to capture delayed biomarker elevations.